Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000461
Status:
COMPLETED
Last Update Posted:
2016-03-16
First Post:
1999-10-27
Brief Title:
Harvard Atherosclerosis Reversibility Project HARP
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2005-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine by sequential coronary arteriography whether a lipid-lowering diet with and without lipid-lowering drugs could reverse coronary artery disease in normocholesterolemic patients Also to test whether fish oil supplements could improve human coronary atherosclerosis Finally to determine the effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and normal cholesterol levels At least three clinical trials were conducted
Detailed Description:
BACKGROUND
The prognosis of patients with coronary heart disease is closely related to the degree of coronary luminal obstruction In population studies the incidence and severity of coronary atherosclerosis on angiography is correlated with diet and plasma lipoprotein cholesterol Previous clinical trials had shown that treatments that lowered plasma concentrations of low density lipoprotein cholesterol benefited some hypercholesterolemic patients with coronary heart disease No similar benefit had been demonstrated in normocholesterolemic patients who make up the majority of patients with coronary heart disease
DESIGN NARRATIVE
In the cholesterol-lowering agent trial all patients received Step 1 dietary instruction before randomization and every three months thereafter Randomization was stratified by medical or surgical treatment for coronary disease and the ratio of total to HDL cholesterol A total of 39 patients were assigned to placebo and 40 to active treatment with pravastatin nicotinic acid cholestyramine and gemfibrozil stepwise as needed to reach the specified goal total cholesterol less than or equal to 41 mmolL ratio of LDLHDL cholesterol less than or equal to 20 Lipid concentrations were measured every six weeks Baseline angiograms were compared to angiograms taken at 30 months
In the fish oil trial 41 patients were randomized to fish oil capsules containing 6 grams of n-3 fatty acids daily and 39 patients were randomized to olive oil placebo capsules for an average duration of 28 months Each fish oil capsule contained 500 mg of n-3 polyunsaturated fatty acids composed of 240 mg of eicosapentaenoic acid 160 mg of docosahexaenoic acid and 100 mg of mainly docosapentaenoic acid Randomization was stratified by medical or surgical treatment for coronary disease and the ratio of total to HDL cholesterol The primary outcome variable was change in minimal diameter of coronary artery lesions expressed as a continuous variable During the initial hospital stay for catheterization dietary instruction was provided to every patient according to the National Cholesterol Education Program NCEP Step 1 guidelines A seven-day diet record was collected at the randomization visit and every three months during the trial Every twelve weeks a research nurse reviewed with the patients side effects diet and concomitant medications and performed a pill count Every 24 weeks the patients received an interval medical history and physical examination by a physician A fasting blood sample was obtained for lipid analysis at the 12- and 24-week visits and every 24 weeks thereafter If the total cholesterol level of any patient increased to 250 mgdl 643 mmolliter or greater on two consecutive measurements intensified dietary instruction was given followed by drug therapy with cholestyramine or nicotinic acid or both as needed to lower total cholesterol to less than 250 mgdl Twenty-one patients did not complete the protocol due to death refusal to undergo the second cardiac catheterization development of medical conditions precluding participation intolerance to the capsules and a missing initial angiogram
In the combination therapy trial patients were randomized to usual care or to stepped-care drug therapy with lipid-lowering agents including pravastatin nicotinic acid cholestyramine and gemfibrozil to decrease total cholesterol levels to less than 160 mgdl and the ratio of low density lipoprotein cholesterol to high density lipoprotein cholesterol to less than 20 Measurements included fasting serum lipoprotein profile fasting apolipoprotein levels and frequency of adverse effects Patients were assessed every six weeks during drug titration and every three months thereafter for two -and-a-half years
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
The prognosis of patients with coronary heart disease is closely related to the degree of coronary luminal obstruction In population studies the incidence and severity of coronary atherosclerosis on angiography is correlated with diet and plasma lipoprotein cholesterol Previous clinical trials had shown that treatments that lowered plasma concentrations of low density lipoprotein cholesterol benefited some hypercholesterolemic patients with coronary heart disease No similar benefit had been demonstrated in normocholesterolemic patients who make up the majority of patients with coronary heart disease
DESIGN NARRATIVE
In the cholesterol-lowering agent trial all patients received Step 1 dietary instruction before randomization and every three months thereafter Randomization was stratified by medical or surgical treatment for coronary disease and the ratio of total to HDL cholesterol A total of 39 patients were assigned to placebo and 40 to active treatment with pravastatin nicotinic acid cholestyramine and gemfibrozil stepwise as needed to reach the specified goal total cholesterol less than or equal to 41 mmolL ratio of LDLHDL cholesterol less than or equal to 20 Lipid concentrations were measured every six weeks Baseline angiograms were compared to angiograms taken at 30 months
In the fish oil trial 41 patients were randomized to fish oil capsules containing 6 grams of n-3 fatty acids daily and 39 patients were randomized to olive oil placebo capsules for an average duration of 28 months Each fish oil capsule contained 500 mg of n-3 polyunsaturated fatty acids composed of 240 mg of eicosapentaenoic acid 160 mg of docosahexaenoic acid and 100 mg of mainly docosapentaenoic acid Randomization was stratified by medical or surgical treatment for coronary disease and the ratio of total to HDL cholesterol The primary outcome variable was change in minimal diameter of coronary artery lesions expressed as a continuous variable During the initial hospital stay for catheterization dietary instruction was provided to every patient according to the National Cholesterol Education Program NCEP Step 1 guidelines A seven-day diet record was collected at the randomization visit and every three months during the trial Every twelve weeks a research nurse reviewed with the patients side effects diet and concomitant medications and performed a pill count Every 24 weeks the patients received an interval medical history and physical examination by a physician A fasting blood sample was obtained for lipid analysis at the 12- and 24-week visits and every 24 weeks thereafter If the total cholesterol level of any patient increased to 250 mgdl 643 mmolliter or greater on two consecutive measurements intensified dietary instruction was given followed by drug therapy with cholestyramine or nicotinic acid or both as needed to lower total cholesterol to less than 250 mgdl Twenty-one patients did not complete the protocol due to death refusal to undergo the second cardiac catheterization development of medical conditions precluding participation intolerance to the capsules and a missing initial angiogram
In the combination therapy trial patients were randomized to usual care or to stepped-care drug therapy with lipid-lowering agents including pravastatin nicotinic acid cholestyramine and gemfibrozil to decrease total cholesterol levels to less than 160 mgdl and the ratio of low density lipoprotein cholesterol to high density lipoprotein cholesterol to less than 20 Measurements included fasting serum lipoprotein profile fasting apolipoprotein levels and frequency of adverse effects Patients were assessed every six weeks during drug titration and every three months thereafter for two -and-a-half years
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL036392 | NIH | None | httpsreporternihgovquickSearchR01HL036392 |